Hypolipidemic activity of rifamycin derivatives.
Series of 3-piperidinyl- and 3-piperazinylrifamycins and to a certain extent 3-hydrazonorifamycins all bearing lipophilic side chains were found to exert potent hypolipidemic activity in lowering both serum cholesterol and LDL-cholesterol in rats. Starting from 3-[N'-(2,4,6-trimethylbenzyl)-N-piperazinyl]rifamycin SV (compound 25), a series of derivatives were synthesized with the aim of dissociating the hypolipidemic from the antibacterial activity, leading to the 8-O,N-dipivaloyl derivative of 25 (compound 48), which is devoid of any antibacterial activity but shows about 50-60% reduction of LDL-cholesterol and 20-30% reduction of serum cholesterol at a dose of 10 mg/kg. Compound 48 was selected for further pharmacological evaluation.
Traxler
P
P
Pharmaceuticals Research Laboratories, Ciba-Geigy, Ltd., Basle, Switzerland.
Kump
W
W
Mueller
K
K
Tosch
W
W
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors; D000960:Hypolipidemic Agents / Q000138:chemical synthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D012294:Rifamycins / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000960:Hypolipidemic Agents; D012294:Rifamycins; D012321:DNA-Directed RNA Polymerases